Glucagon Clearance Is Preserved in Type 2 Diabetes
Magnus F.G. Grøndahl, Asger Lund, Jonatan I. Bagger, Tonny Studsgaard Petersen, Nicolai J. Wewer Albrechtsen, Jens J. Holst, Tina Vilsbøll, Mikkel Christensen, Filip K. Knop
Diabetes, Vol. 71, Issue 1, pp. 73–82 (2021)
10.2337/db21-0024
PMID: 34702780
Abstract
Hyperglucagonemia is a common observation in both obesity and type 2 diabetes, and the etiology is primarily thought to be hypersecretion of glucagon. We investigated whether altered elimination kinetics of glucagon could contribute to the hyperglucagonemia in type 2 diabetes and obesity. Individuals with type 2 diabetes and preserved kidney function (8 with and 8 without obesity) and matched control individuals (8 with and 8 without obesity) were recruited. Each participant underwent a 1-hour glucagon infusion (4 ng/kg/min), achieving steady-state plasma glucagon concentrations, followed by a 1-hour wash-out period. Plasma levels, the metabolic clearance rate (MCR), half-life (T½) and volume of distribution of glucagon were evaluated and a pharmacokinetic model was constructed. Glucagon MCR and volume of distribution were significantly higher in the type 2 diabetes group compared to the control group, while no significant differences between the groups were found in glucagon T½. Individuals with obesity had neither a significantly decreased MCR, T½, nor volume of distribution of glucagon. In our pharmacokinetic model, glucagon MCR associated positively with fasting plasma glucose and negatively with body weight. In conclusion, our results suggest that impaired glucagon clearance is not a fundamental part of the hyperglucagonemia observed in obesity and type 2 diabetes.
Topics
Field: Medicine · Subfield: Endocrinology, Diabetes and Metabolism
Keywords
Type 2 diabetes,Glucagon,Medicine,Internal medicine,Endocrinology,Diabetes mellitus,Insulin
UN Sustainable Development Goals
- Good health and well-being (0.74)
All Available Versions
- Landing page — Diabetes publishedVersion
- Landing page — PubMed publishedVersion
- Landing page — PubMed publishedVersion
- Landing page — Research at the University of Copenhagen (University of Copenhagen) submittedVersion
Citations by Year
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| 2 | 6 | 3 | 5 | 1 |
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- Classification and Diagnosis of Diabetes Mellitus and Other Categories of Glucose Intolerance 1979 · 4954
- Changes in Gut Microbiota Control Metabolic Endotoxemia-Induced Inflammation in High-Fat Diet–Induced Obesity and Diabetes in Mice 2008 · 4808
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